activity and weak although possibly significant antihistamine activity; as such, side effects of iprindole are much less prominent relative to other TCAs, and it is well tolerated. However, iprindole may not be as effective as other TCAs, particularly in terms of anxiolysis. Based on animal research, the antidepressant effects of iprindole may be mediated through downstream dopaminergic mechanisms. The binding affinities of iprindole for various biological targets are presented in the table to the right. It is presumed to act as an inhibitor or antagonist/inverse agonist of all sites. Considering the range of its therapeutic concentrations (e.g., 63–271 nM at 90 mg/day), only the actions of iprindole on the 5-HT2 and histamine receptors might be anticipated to be of possible clinical significance. However, it is unknown whether these actions are in fact responsible for the antidepressant effects of iprindole. The plasma protein binding of iprindole and hence its free percentage and potentially bioactive concentrations do not seem to be known. Pharmacokinetics Only one study appears to have evaluated the pharmacokinetics of iprindole. A single oral dose of 60 mg iprindole to healthy volunteers has been found to achieve mean peak plasma concentrations of 67.1 ng/mL (236 nmol/L) after 2 to 4 hours. The mean terminal half-life of iprindole was 52.5 hours, which is notably much longer than that of other TCAs like amitriptyline and imipramine. Following chronic treatment with 90 mg/day iprindole for 3 weeks, plasma concentrations of the drug ranged between 18 and 77 ng/mL (63–271 nmol/L). Theoretical steady-state concentrations should be reached by 99% within 15 to 20 days of treatment. Chemistry Iprindole is a tricyclic compound, specifically a cyclooctaindole (that is, an indole nucleus joined with a cyclooctyl ring), and possesses three rings fused together with a side chain attached in its chemical structure. It is a tertiary amine TCA, although its ring system and pharmacological properties are very different from those of other TCAs. Other tertiary amine TCAs that are similar to iprindole include butriptyline and trimipramine. The chemical name of iprindole is 3-(6,7,8,9,10,11-hexahydro-5H-cycloocta[b]indol-5-yl)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H28N2 with a molecular weight of 284.439 g/mol. The drug has been used commercially as both the free base and the hydrochloride salt. The CAS Registry Number of the free base is 5560-72-5 and of the hydrochloride is 20432-64-8. History Iprindole was developed by Wyeth and was marketed in 1967. Society and